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Relatia Dintre Arteroscleroza Si Colesterol Seric PDF
Relatia Dintre Arteroscleroza Si Colesterol Seric PDF
Relatia Dintre Arteroscleroza Si Colesterol Seric PDF
BackgroundThe relation between serum lipids and risk of coronary events has been established, but there are no data
demonstrating directly the relation between serum low-density lipoprotein (LDL) cholesterol and high-density
lipoprotein (HDL) cholesterol versus serial changes in coronary plaque dimensions.
Methods and ResultsWe performed standard analyses of serial intravascular ultrasound (IVUS) studies of 60 left main
coronary arteries obtained 18.39.4 months apart to evaluate progression and regression of mild atherosclerotic plaques
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in relation to serum cholesterol levels. Overall, there was (1) a positive linear relation between LDL cholesterol and the
annual changes in plaque plus media (P&M) cross-sectional area (CSA) (r0.41, P0.0001) with (2) an LDL value of
75 mg/dL as the cutoff when regression analysis predicted on average no annual P&M CSA increase; (3) an inverse
relation between HDL cholesterol and annual changes in P&M CSA (r0.30, P0.02); (4) an inverse relation
between LDL cholesterol and annual changes in lumen CSA (r0.32, P0.01); and (5) no relation between LDL and
HDL cholesterol and the annual changes in total arterial CSA (remodeling). Despite similar baseline IVUS
characteristics, patients with an LDL cholesterol level 120 mg/dL showed more annual P&M CSA progression and
lumen reduction than patients with lower LDL cholesterol.
ConclusionsThere is a positive linear relation between LDL cholesterol and annual changes in plaque size, with an LDL
value of 75 mg/dL predicting, on average, no plaque progression. HDL cholesterol shows an inverse relation with annual
changes in plaque size. (Circulation. 2003;108:2757-2762.)
Key Words: ultrasonics coronary disease cholesterol lipids
Received May 28, 2003; revision received September 4, 2003; accepted September 8, 2003.
From the Department of Cardiology, Essen University, Essen, Germany (C.v.B., M.H., D.B., A.S., R.E.); the Department of Cardiology, Medisch
Spectrum Twente, Enschede, the Netherlands (C.v.B.); and the Cardiovascular Research Foundation, New York, NY (G.S.M.).
Correspondence to Dr Clemens von Birgelen, Medisch Spectrum Twente, Enschede Hospital, Cardiology Department, Ariensplein 1, 7511 JX
Enschede, The Netherlands. E-mail von.birgelen@freeler.nl
2003 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org DOI: 10.1161/01.CIR.0000103664.47406.49
2757
2758 Circulation December 2, 2003
Methods matching of the target site on initial and follow-up IVUS studies was
ensured by use of side-by-side comparison of the serial IVUS video
Study Population sequences along with information of the pullback speed; the opera-
We analyzed serial IVUS studies of 60 LM coronary artery athero- tors recorded comments (on videotape); and characteristic calcifi-
sclerotic plaques during 12 months of follow-up (18.39.4 cations, vascular and perivascular landmarks, and plaque shapes. If
months). All patients were examined in the Essen University Cardiac required, x-ray sequences of the dedicated image-in-image system
Catheterization Laboratory. All plaques were de novo, were hemo- (Echo-Map) were revisited to optimize matching.17
dynamically nonsignificant, and met the following criteria: (1) serial The lumen CSA was measured by tracing the leading edge of the
high-quality IVUS of the entire LM 12 months apart, (2) calcifi- intima. The EEM CSA was measured by tracing the leading edge of
cations that did not limit quantitative assessment of vessel cross- the adventitia. In our laboratory, the intraclass correlation coefficient
sectional area (CSA), (3) nonostial plaque location, (4) angiographic is 0.99 for repeated measurements of EEM, 0.96 for lumen, and 0.99
lumen diameter stenosis 30% (worst view visual assessment), for P&M CSA. Plaque burden (%) was calculated as (P&M divided
and (5) no intervention in the very proximal left anterior descending by EEM)100%. To compensate for variations in follow-up inter-
or circumflex coronary arteries, because these interventions could vals and to obtain comparable data, we calculated absolute and
have affected the LM artery. This IVUS study was approved by the relative changes () between initial and follow-up IVUS data;
Local Council on Human Research. All patients signed a written measurements were normalized for the length of the follow-up
informed consent form as approved by the Local Medical Ethics period (changes per year) and for baseline measurements. In analogy
Committee. with 1 previous coronary progression-regression study,18 we used an
LDL cholesterol threshold of 120 mg/dL to compare patients with
Cardiovascular Risk Factors, Clinical Data, LDL cholesterol 120 mg/dL (group A) versus those with LDL
and Medication cholesterol 120 mg/dL (group B).
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Figure 1. Annual changes of IVUS parameters in group A (LDL Figure 3. Relation between LDL cholesterol and annual changes in
cholesterol 120 mg/dL) vs group B (LDL cholesterol 120 P&M CSA. An LDL value of 75 mg/dL was the cutoff at which
mg/dL) plaques. regression analysis predicts no average annual P&M CSA increase.
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no average annual plaque increase (Figure 3). However, Cholesterol and Serial IVUS Data in Patients
individual patients exhibited plaque increase even at lower Treated With Statins
LDL cholesterol values. Similarly, a value of the LDL/HDL When only those patients who were on statins were analyzed
ratio of 1.3 was the cutoff at which regression analysis (n49), there was still a significant positive linear relation
predicted no average annual plaque increase. between percent annual changes in P&M CSA versus LDL
Figure 2. Relation between LDL cholesterol (left), HDL cholesterol (middle), and LDL/HDL ratio (right) vs serial IVUS data.
von Birgelen et al Plaque Progression-Regression and Cholesterol 2761
cholesterol (r0.45, P0.001) and a negative linear relation Our present study suggests that an LDL cholesterol value of
between annual changes in P&M CSA versus HDL choles- 75 mg/dL is on average associated with no plaque progres-
terol (r0.30, P0.05). An LDL value of 72.5 mg/dL was sion. Importantly, because ethnic factors may influence the
the cutoff at which regression analysis predicted no average response to serum cholesterol levels,31 the results of our study
annual P&M CSA increase. Percent annual changes in lumen may apply only to white patients.
CSA tended to show a negative linear relation with LDL Our study did not address pharmacological intervention
cholesterol (r0.25, P0.12), but there was no relation (lipid lowering) but rather was a clinical observational study
with HDL cholesterol (r0.14, y0.18x6.6; P0.35). in patients with coronary artery disease treated by conven-
Moreover, there was no relation between either LDL or HDL tional medical therapy, including statins in the vast majority
cholesterol and annual changes in EEM CSA (r0.02 for of patients. The nature of our investigation implies that
both). The number of patients who were not on a statin potential pleiotropic effects of statins could have contributed
(n11) was too small to permit similar meaningful analysis. to our findings32; however, the data are not currently available
to permit further subanalyses to exclude the effect of statins.
Discussion Nevertheless, when we analyzed only those patients who
We found (1) a positive linear relation between LDL choles- were on a statin, the relations between LDL cholesterol and
terol and annual changes in P&M area with (2) an LDL value HDL cholesterol versus the percent annual changes in plaque
of 75 mg/dL as the cutoff at which regression analysis size remained unchanged.
predicted, on average, no annual P&M area increase; (3) an Baseline total arterial CSA was identical in patients with
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inverse relation between HDL cholesterol and annual changes higher (120 mg/dL) versus lower LDL cholesterol but was
in P&M area; and (4) no relation between either LDL or HDL (for both groups) significantly larger than that of a historic
cholesterol and annual changes in total arterial area (ie, population of nondiseased LM coronary arteries.11 This
arterial remodeling). Because LDL and HDL cholesterol suggests that, at baseline, plaques in both groups were already
levels did not appear to affect arterial remodeling, there was accompanied by positive (compensatory) arterial remodel-
an inverse relation between LDL cholesterol and annual ing.11,12 Moreover, both groups had a slight but similar further
changes in lumen area. Finally, although they had similar increase in total arterial area not related to LDL or HDL
IVUS characteristics at baseline, patients with LDL choles-
cholesterol levels. The variability of remodeling responses12
terol 120 mg/dL showed more annual plaque progression
may partially explain progressive lumen narrowing in some
and lumen reduction than did patients with lower LDL
(but not all) individuals despite an effective modification of
cholesterol values.
the lipid profile.24 This is in contrast to one histopathological
study showing a modest linear relationship between HDL
Serial Plaque and Lumen Changes and Cholesterol
There is ample accumulated evidence of the significance of cholesterol and positive remodeling assessed at a single time
cholesterol on the progression of atherosclerosis.19 21 The point.33
present linear relations between LDL cholesterol and both
P&M progression and lumen reduction agree with previous Limitations
studies, and they emphasize the importance of lowering total Although by most standards, this was a large serial IVUS
cholesterol and LDL cholesterol for preventing disease pro- study, all studies with long-term serial assessment of athero-
gression.1 4,2224 The inverse relation between HDL choles- sclerosis are limited to a relatively small number of patients.
terol and IVUS P&M progression in the present study is also The data of this study are unique and may well reflect clinical
in good agreement with previous studies25,26 that underlined reality. However, because retrospective analyses of prospec-
the importance of increasing HDL cholesterol levels. tively acquired data (demographics, medication, and labora-
Previous large (nonserial) histopathological studies have tory tests) were performed, we cannot rule out a certain
demonstrated the relation between serum cholesterol and selection bias; we were able to include only patients with
atherosclerotic disease severity27,28 and plaque vulnerabili- significant coronary artery disease who were admitted for
ty.29 Our study extends these previous observations by repeat cardiac catheterization 12 months after baseline (this
providing serial morphological evidence for the clinically limitation applies to both groups). Therefore, the findings of
established relation between disease progression and serum the present study may not be applicable to the general
lipids. population. We used 2 IVUS systems in the present study;
Previous serial IVUS studies in native coronary arteries did however, when we compared the data from the 2 different
not address the relation between cholesterol levels and plaque IVUS systems, we found no differences, and separate linear
progression. These IVUS studies compared treatment with a regression analyses in data sets that were obtained by one or
particular statin versus dietary stabilization or usual care.1315 the other IVUS system provided almost identical results.
Cholesterol lowering is an accepted principle in reducing Furthermore, individual patients were imaged with the same
the risk of coronary artery disease, and the extent to which system at index and follow-up. 3D (ECG-gated) IVUS
cholesterol is lowered appears to be important. In addition, a analysis34 may be superior for the assessment of coronary
greater reduction of LDL cholesterol is associated with a dimensions and provides volumetric data. In addition, sophis-
greater reduction in the risk of cardiovascular events, but ticated computer-aided gray-scale IVUS analyses15 or radio-
clinical studies have not determined definitively whether frequency IVUS analyses35 may be superior to visual IVUS
there is a benefit in lowering cholesterol to very low levels.30 analysis of plaque composition.
2762 Circulation December 2, 2003
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Relation Between Progression and Regression of Atherosclerotic Left Main Coronary
Artery Disease and Serum Cholesterol Levels as Assessed With Serial Long-Term ( 12
Months) Follow-Up Intravascular Ultrasound
Clemens von Birgelen, Marc Hartmann, Gary S. Mintz, Dietrich Baumgart, Axel Schmermund
and Raimund Erbel
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